Clostridium difficile is a common nosocomial pathogen. By far the most common cause of infectious diarrhea in hospitalized patients in North America, there has been an alarming rise in incidence of C. difficile infection (CDI) since 2000. This rise has been accompanied by increasing rates of severe disease resulting in colectomy and/or death. Equally as concerning has been the increased incidence of community-associated CDI which has been reported in populations previously believed to be low risk. A common management problem in CDI is relapse, which occurs in up to 20% of patients after treatment of the initial infection. Patients who experience 1 recurrence have a 40% risk of further relapse and those with 2 or more episodes face a 60% risk. While the first relapse is generally treated with a second course of metronidazole or vancomycin, current guidelines recommend a tapering course of oral vancomycin, which is typically given over 4-8 weeks at a cost of $3500, after a second recurrence. Unfortunately, treatment options are limited for those patients who develop further recurrences. A number of patients become vancomycin dependent, developing CDI relapse whenever this antibiotic is stopped. Antimicrobial agents are thought to alter the normal bacterial flora of the gastrointestinal tract so as to permit colonization and/or proliferation and toxin elaboration by C. difficile. The specific antimicrobials used to treat CDI also may predispose patients to further relapses through the maintenance of perturbed intestinal flora and may contribute to the emerging problems of drug resistance. Fecal microbiota transplantation (FMT) involves administration of feces from a healthy individual into a patient with relapsing CDI to promote recolonization with missing components of normal intestinal flora. The literature is limited to individual cases and case series, but these reported experiences with nearly 300 cases shows that FMT has cured relapsing CDI in a mean of 89% of patients treated. FMT appears to be safe, with no adverse effects or complications yet described, durable and inexpensive. To date there has not been a published prospective clinical trial of FMT for CDI. There is a need for research documenting efficacy as well as patient safety and tolerability. Standard treatment protocols also need to be developed. We propose to conduct a randomized, controlled clinical trial of FMT delivered at colonoscopy for treatment of relapsing CDI with the goal of establishing efficacy and safety data. This study includes collaboration with an investigator who will analyze the complex bacterial communities in stool collected from our subjects (before and after FMT) and their donors. Given the increasing incidence and severity of CDI, the problem of recurrent disease in a significant number of patients and the economic burden and drug-resistant infections associated with long- term use of oral vancomycin, it is important to determine whether FMT is effective for treatment of relapsing CDI. PUBLIC HEALTH RELEVANCE: There has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in North America over the past decade. Relapsing infection is a common problem in patients treated for CDI, often requiring prolonged and expensive courses of oral vancomycin with limited alternative treatment options. This study will determine if fecal microbiota transplantation, which involves administering fecal flora from a healthy stool donor to a patient with relapsing CDI, is an effective and safe treatment.